Rate of cognitive decline before seizure diagnosis in individuals with dementia and seizures

Abstract

AbstractBackgroundSeizures and epilepsy occur frequently in individuals diagnosed with dementia. While previous studies report highest incidence in advanced disease stages, emerging studies suggest subclinical seizures noted only on Magnetoencephalography or electroencephalography(EEG) occur frequently in early stages. Such recorded subclinical seizure activity is associated with a more rapid course of cognitive decline on longitudinal assessment. We thus hypothesized individuals with dementia who are diagnosed with seizures in any stage experience a rapid cognitive decline before they are diagnosed with seizures.MethodStudy design is a retrospective case‐control study, assessing clinical data from 24142 research subjects evaluated longitudinally from the National institute of health Alzheimer Coordination Center, years 2006‐2019. Seizures diagnosed during follow up were used as a predicting variable. Individuals with seizures on their first visit as well as individuals with unknown seizure status were excluded. Individuals with unknown APOE genotype and those without longitudinal data were also excluded. We assessed cognitive decline as an outcome using annual Mini Mental State Exam (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR‐SB). We assessed the decline using a linear mixed effects models adjusting for other variables known to alter decline rate such as age at onset of symptoms, sex and ApoE4 genotype and included a random effect for time between visits within patients.ResultWe identified 205 and 4667 individuals with and without seizures respectively on follow up research visits. Patients with seizures had an younger mean age at symptom onset (65±11.3 vs 70±10.0), of similar sex (50.0% and 50.7% male) and remained longer on follow up (5±3 vs 3±2). Baseline MMSE and CDR‐SB was similar in both groups. Compared to subjects without seizures, those with seizures had a rapid annual decline in CDR‐SB (0.98, SE 0.24, 95% CI 0.51‐1.46, p<.0001) and MMSE (‐1.8, SE = .40, 95% CI ‐1.4 and ‐2.6, p<0.00001).ConclusionA rapid rate of decline can be observed in individuals with dementia prior to seizure diagnosis. Our study suggests undiagnosed seizures or seizures activity on EEG should be suspected in individuals who experience a rapid rate of cognitive decline.